• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late-onset progressive degeneration.

To test the hypothesis that inhibition of axonal transport is sufficient to cause motor neuron degeneration such as that observed in amyotrophic lateral sclerosis (ALS), we engineered a targeted disruption of the dynein-dynactin complex in postnatal motor neurons of transgenic mice. Dynamitin overexpression was found to disassemble dynactin, a required activator of cytoplasmic dynein, resulting in an inhibition of retrograde axonal transport. Mice overexpressing dynamitin demonstrate a late-onset progressive motor neuron degenerative disease characterized by decreased strength and endurance, motor neuron degeneration and loss, and denervation of muscle. Previous transgenic mouse models of ALS have shown abnormalities in microtubule-based axonal transport. In this report, we describe a mouse model that confirms the critical role of disrupted axonal transport in the pathogenesis of motor neuron degenerative disease.

Pubmed ID: 12062019

Authors

  • LaMonte BH
  • Wallace KE
  • Holloway BA
  • Shelly SS
  • AscaƱo J
  • Tokito M
  • Van Winkle T
  • Howland DS
  • Holzbaur EL

Journal

Neuron

Publication Data

May 30, 2002

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM48661
  • Agency: NIGMS NIH HHS, Id: GM56707

Mesh Terms

  • Amyotrophic Lateral Sclerosis
  • Animals
  • Axonal Transport
  • Axons
  • Cell Death
  • Disease Models, Animal
  • Dyneins
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Microtubule-Associated Proteins
  • Motor Neurons
  • Muscular Atrophy
  • Neurofilament Proteins
  • Phenotype
  • Spinal Cord
  • Spinal Nerve Roots
  • Up-Regulation